Since the 1960s the field of gut endocrinology has undergone a period of rapid growth. An ever increasing number of active peptides are being discovered in tissue structures ranging from classical endocrine cells to autonomic nerve fibres. The peptides found in nerve fibres in the gastroenteropancreatic tract have been called the gut neuropeptides; these include VIP, substance P and enkephalins. It was the localisation of these substances which formed the basis of this study. The purpose of this work was to apply and, where necessary, adapt immunocytochemical techniques in order to examine the distribution of the peptides in the nerves of the mammalian gut and pancreas, in both normal and disease states and to test the hypothesis that the peptide containing nerves undergo identifiable changes in some diseases. An extended series of experiments established a new method for preparing tissue for immunocytochemical investigation. The distribution of the peptide containing nerves was studied in a wide range of mammalian species, particularly man and the various different types were found in each species, at all levels of the gut and in each layer of the wall. In the pancreas, peptide containing nerves were found in association with both the endocrine and the exocrine tissue. Following the localisation of peptides to nerves in normal tissues, pathological specimens were studied from a number of different gut diseases. Distinct abnormalities of the nerves were detected. For example, changes were found in both congenital and acquired megacolon where peptide containing nerves were reduced in number. In contrast, in Crohn's disease one particular group of nerves, those containing VIP, was found to be hyperplastic. In addition to examining the distribution of the peptides, the occurrence of two so-called 'brain specific' proteins was investigated in the gut and pancreas. Immunostaining of one of the proteins, an enzyme originally but erroneously called neuron specific enolase (NSE), was shown to be a specific means for the demonstration of all known endocrine cells and nerves of the gut and pancreas. The other protein, S-100, has no known function but has a widespread distribution in glial and Schwann cells. It was therefore used as a marker for these elements in normal and diseased tissues.